Although dysthymic disorders and related forms of chronic depression constitute a substantial public health problem, they are poorly understood in terms of natural history, diagnostic characteristics and response to various types of treatment. We have been gathering pilot data about the clinical characteristics of outpatients with chronic depressions, and are conducting the first placebo-controlled trial of short-term antidepressant treatment (six weeks) using imipramine (IMI). Our pilot data on diagnostic characteristics have already influenced the revised criteria for Dysthymic Disorder in DSM-III-R. We have also found a substantial medication effect- 13/22 (59%) of IMI vs. 3/24 (13%) of placebo treated patients have been classified as responders upon completion of double-blind treatment. Open continuation therapy in the IMI responders resulted in 86% of continued favorable response after six months. Social vocational dysfunction was also more significantly improved among IMI than placebo-treated subjects. Based upon these promising results, the current application proposes to: 1) test the effectiveness of long- term treatment for chronic depression in a two-year maintenance using another TCA-DMI vs. placebo in responders to acute treatment, 2) explore the additional effectiveness of combined psychotherapy/pharmacotherapy by adding Interpersonal Therapy (IPT) to enhance the effect of DMI in patients who fail to recover after 10 weeks of DMI alone, 3) compare demographic and diagnostic characteristics of two groups of patients having a) early-age onst DSM III Dysthymic Disorders vs. b) acute Major Depressive Disorders. Areas of assessment will include demographic characteristics, comorbid DSM III Axis I and Axis II disorders, psychosocial stress, social-vocational function and family history, 4) examine diagnostic stability (test-retest reliabiltity) of the diagnoses of Dysthymic Disorder and Major Depressive Disorder, 5) to study the (concurrent) validity of diagnosis in these groups of patients by independent blind interview of a close relative. Results from our treatment studies demonstrated that a substantial proportion of chronically depressed outpatients responded to short-term treatment with TCA, and suggest that longer-term treatment be indicated and effective. If the long-term maintenance study show TCA treatment prevents relapse, a major contribution to the treatment of this important clinical problem will be realized. We are also developing a diagnostic set that will help to refine methods of classifying chronic depression.